Vitamin B12, in the form of its coenzyme, is a cofactor for a remarkable series of enzyme-catalyzed transformations. Of these, three enzymes: beta-methylaspartate mutase, methylmalonyl-CoA mutase and beta-methylitaconate mutase are of particular interest because they catalyze a carbon-skeleton rearrangement for which there has been no analogy in organic chemistry. In this proposal we present a new chemical model reaction in which methylitaconate attached through its methyl group to the cobalt atom of vitamin B12 has been found to rearrange spontaneously to alpha-methyleneglutarate. This is the first observation of a B12 rearrangement occurring in the absence of any enzyme. It signals a much stronger chemical and biochemical role for the cofactor than has hitherto been imagined possible. It is proposed to take advantage of this novel finding in a number of ways. Istopic labelling studies and determination of the absolute configuration of the rearrangement reaction will be used to probe the degree of congruence between the model reaction and the enzyme reaction. Other square-planar cobalt complexes including degradation products of vitamin B12 will be examined in an effort to determine the limits of activity as it is related to structure. Possible intermediates in the model reaction will be tested using spectroscopic techniques such as electron spin resonance and ultraviolet spectroscopy, as well as by chemical trapping techniques. It is highly desirable, both in order to establish the generality of our findings as well as to learn more about vitamin B12, to examine the other two carbon-skeleton rearrangements in this series. Efforts directed to this end will be initiated.